Immuno-oncology in head and neck squamous cell carcinoma - a narrative review

Immuno-oncology studies the immune system in cancer. In recent decades, immunotherapy has shown a good response to the treatment of various locally advanced and metastatic cancers. The main mechanisms of action include stimulation of the patient's own immune system to enhance immune responses acting in tumor escape pathways. This review examined the literature related to immune system mechanisms in head and neck squamous cell carcinoma (HNSCC) and their application in immunotherapy using biomarkers. The PUBMED, LILACS, MEDLINE, WHOLIS, and SCIELO databases were searched using the terms squamous cell carcinoma, head and neck, immuno-oncology, immunotherapy, and immunology. The main drugs currently available for clinical use in patients diagnosed with HNSCC include pembrolizumab and nivolumab, both classified as check-point inhibitors. These immunobiological agents improve patient survival and quality of life. Many authors and clinical trials point out that the recommendation of these agents is linked to the dose of PD-L1 (ligand expressed primarily by tumor cells), which proved to be an unreliable biomarker in the patient selection. Recommendation of immunotherapy depends on reliable biomarkers that must be identified in order to achieve good therapeutic results.

Influence of acute renal failure on the mononuclear phagocytic system

Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung) of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g) were divided into three groups (N = 5): group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05). Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05). Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98) and lung (2.63), and a higher level in the liver (105.51) than control. Group III animals showed a lower level of radioactivity in the spleen (11.94) and a higher level in the liver (61.80), lung (11.30) and blood clot (5.13) than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system

Effect of sodium carboxymethylcellulose and methylprednisolone on the healing of jejunal anastomoses in rats

Sodium carboxymethylcellulose (SCMC) has been effective in reducing adhesion formation and corticosteroids reduce the inflammatory process. The objective of this study was to define the intraperitoneal (ip) effects of SCMC combined with intramuscular (im) methylprednisolone on peritoneal adhesion formation and on jejunal anastomosis healing in rats. Twenty Wistar rats (200-350 g) were divided into four groups (N = 5): groups I and III (controls) 5 and 21 days of treatment before sacrifice, respectively; groups II and IV (experimental groups) 5 and 21 days of treatment, respectively. SCMC (1 percent) was infused into the abdominal cavity and methylprednisolone (10 mg kg-1 day-1) was injected im daily from the day before surgery for animals of groups II and IV. All rats were submitted to a jejunal anastomosis. Sections of the anastomosis were prepared for routine histopathological analysis. The abdominal adhesion of group IV was less intense when compared with group III (P<0.0008). Anastomotic resistance was higher in groups II and IV when compared with groups I and III, respectively (P<0.05). There was no histological difference between groups I and II (exuberant granulation tissue on the serosal surface). Group III presented little peritoneal fibrinous tissue, with numerous thick collagen fibers. Group IV presented extensive although immature young fibrous tissue with rare thick collagen fibers. Sodium carboxymethylcellulose combined with corticosteroids seemed to diminish peritoneal adhesion but did not reduce anastomotic resistance

Delay in gallbladder emptying during the perimenopausal period

A pilot study has ascribed an important role in gallbladder motility and emptying to the perimenopausal period. To assess the effect of this period on gallbladder emptying and cholelithogenesis, 25 women in the perimenopausal period without gallbladder disease were submitted to cholangiography and two ultrasound exams. The time for gallbladder emptying and the presence of cholelithiasis were assessed. All patients presented a delay in gallbladder emptying with no relationship to the pre- or postmenopausal period. This finding was not related to lithogenesis. Gallbladder emptying time is longer during the perimenopausal period

Endotoxin-induced enteric hypomotility in jaundiced loops in vitro

Biliary obstruction may be accompanied by systemic endotoxemia due to increased growth of enteric microbiota and failure of hepatic clearance mechanisms. This endotoxemia is related to increased postoperative morbidity and mortality. An increased growth of the aerobic flora has been demonstrated experimentally in the presence of biliary obstruction, and in previous studies we observed intestinal hypomotility of jaundiced loops in vitro. To determine the ileal motor response in the presence of jaundice caused by biliary obstruction and in the presence of endotoxemia, an in vitro study was carried out on ileal segments from 10 female Holtzman rats, 2-3 months old, weighing 200 to 300 g, divided into two groups (N = 5): A, washed loops of jaundiced rats, and B, washed loops of jaundiced rats to which endotoxin was added. On the seventh postoperative day, we evaluated the effect of exogenous endotoxin (E. coli 0111:B4, Sigma) on the motor response to acetylcholine of distal ileal segments isolated from both animal groups. A 4-cm ileal segment, located 10 cm from the ileal papilla, was removed and studied in an organ chamber in order to assess dose-response curves to acetylcholine. There was an increase in threshold dose in jaundiced loops with intraluminally injected endotoxin when compared with the loops without intraluminal endotoxin (291 + 188 vs 8.5 + 6.7 muM, P<0.05). The maximum contraction was reduced in jaundiced loops with intraluminal endotoxin in relation to control loops (5.3 + 1.7 vs 18.7 + 4.8 mm, P<0.05), and pD2 was also reduced in jaundiced loops with intraluminal endotoxin in relation to control loops (2.4 + 0.6 vs 3.7 + 0.5, P<0.05). There was no statistical difference between jaundiced loops with and without intraluminal endotoxin when the maximal contraction doses were compared (86 + 66 vs 48 + 22 mM, P>0.05). These results demonstrate that intraluminal endotoxin depressed enteric motility in jaundiced rats.

Consideraçöes sobre a pós-graduaçäo stricto sensu em medicina / Stricto sensu graduation in medicine

Durante os últimos trinta anos, o curso de pós-graduaçao stricto sensu alcançou sua maturidade. O objetivo principal desse curso é formar docentes universitários, atualizando-os em áreas específicas do conhecimento e ensinando-os a produzir trabalhos científicos. Os limites do curso estao relacionados aos poucos orientadores, ao reduzido apoio financeiro e à falta de integraçao com outros cursos e instituiçoes. Os limites relacionados ao corpo discente sao sua disparidade, seu afastamento das atividades profissionais e seu isolamento em um ambiente estranho. Entretanto, as vantagens trazidas por esse curso justificam os investimentos em seu crescimento e conseqüente desenvolvimento da universidade.

Influência dos sais biliares na resposta motora de alças isoladas a acetilcolina, em ratos / Influence of bile salts on the motor response of isolated ileum to acetylcholine, in rats

A ausência de sais biliares na luz intestinal de pacientes com obstruçao biliar tem sido relacionada ao aumento da flora intestinal e maior produçao de endotoxinas, podendo provocar endotoxemia sistêmica. Entretanto, esses sais têm pequena açao sobre a flora aeróbia e facultativa, que pode estar aumentada por alteraçoes motoras intestinais. Objetivo. Avaliar a resposta motora intestinal na obstruçao biliar em presença de sais biliares. Métodos. Estudaram-se in vitro segmentos ileais de 30 ratos Hotzman do sexo feminino divididos em três grupos (n=10): alça lavada; uso de bile intraluminar e uso de sais biliares exógenos por via oral, durante seis dias. Em cada grupo, cinco animais foram submetidos somente a laparotomia, enquanto cinco outros ratos foram submetidos a ligadura do ducto biliar comum. No sétimo dia pós-operatório, retirou-se um segmento ileal de aproximadamente quatro centrímetros, distantes dez centrímetros da papila ileocecal, e que foi estudado por meio de curva dose-resposta a acetilcolina em banho para órgaos isolados. Resultados. Os resultados obtidos mostraram aumento significativo da afinidade pela acetilcolina no grupo com bile intraluminar. Conclusao. A bile intraluminar, aparentemente, exerce efeito modular positivo sobre a motilidade ileal in vitro.

Jejunal absorption of trypsin in rat and guinea pig

Gut absorption is one of the first requirements for the study of the mechanism of a possible anti-inflammatory action of proteases, such as orally administered trypsin. Porcine trypsin absorption was studied in isolated jejunal loops of rats (female Holtzman and male Wistar) and guinea pig (males) by open-loop perfusion. Trypsin was dissolved in Tyrode solution and the solution perfused at a rate of 0.5 ml/min, at 37§C. Trypsin activity, total protein, and sodium and potassium concentrations were assayed in the jejunal effluent; the values were unchanged throughout the experiments, which lasted 45 to 120 min. Using a high sensitivity ELISA (i.e. pg/ml), trypsin absorption could be demonstrated by determination of the enzyme in the mesenteric venous blood (samples of 0.5 ml); the enzyme concentration increased with time of perfusion. The linear range-specificity for intact trypsin varied from 1 to 500 ng/well. In this assay polyclonal antibodies prepared against trypsin-TLCK were utilized. Whereas trypsin concentration in the perfused lumen was practically constant at 0.12 mg/ml, the concentration of absorbed trypsin in mesenteric vein blood increased from about 100 ng/ml at time zero to 1.8 µg/ml, after 45 min of perfusion. Histological and ultrastructural examination of the jejunal mucosa before and after perfusion revealed that the brush-border, basal membrane, and junctional complexes were fully preserved, thus eliminating the possibility that trypsin might have destroyed the structures, thereby reaching the blood circulation. The present data indicate that µg quantities of trypsin were absorbed by the isolated jejunal loop of the rat

Gallstone obstruction of the jejunum

This report illustrates an uncommon source of small bowel ileus. Gallstone obstruction should be considered in elderly women with an acute abdomen. The treatment of choice is always surgical. If the patient does not present other biliary diseases, the withdrawal of the calculi should be the only procedure.

Avaliacao radiologica e eletromanometrica da acao do bromopride sobre o esvaziamento gastrico e pressao do esfincter inferior do esofago no pos-operatorio imediato da cirurgia para ulcera duodenal. / Radiological and electromanometrical evaluation of the action of bromopride on gastric emptying and lower esophageal sphincter pressure in the immediate postoperative period of duodenal ulcer surgery

Estudou-se o efeito do bromopride sobre o esvaziamento gastrico e pressao do esfinger inferior do esofago, em 18 pacientes, portadores de ulcera duodenal complicada e submetidos a vagotomia troncular ou seletiva (9 de cada) mais antrectomia e gastroduodenostomia na pequena curvatura. Em dez daqueles pacientes, a dosagem de 10 mg IM de bromopride, de 8 em 8 horas nao produziu alteracoes significativas da pressao do esfincter inferior do esofago e do esvaziamento gastrico, em relacao a dez controles tratados pela mesma tecnica, provavelmente porque os niveis sanguineos eram insuficientes, uma vez que os exames eram feitos varias horas apos a aplicacao da droga. Nos outros oito pacientes a pesquisa foi realizada 30 minutos apos a injecao IM de bromopride, constatando-se que a pressao do esfincter inferior do esofago apresentou valores significativamente maiores em relacao ao mesmo exame feito no mesmo paciente, mas sem a acao da droga.Nao houve diferenca significativa no esvaziamento gastrico, admitindo-se que isto seja devido a dificuldade em se avaliar pequenas modificacoes nesse parametro porque nao ha condicoes de se provocar o esvaziamento subito de um estomago hipotonico, a nao ser por meios mecanicos

Acompanhamento radiologico dos pos-operatorios imediatos de pacientes operados de ulcera cloridropeptica por vagotomia, antrectomia parcial e anastomose gastroduodenal na pequena curvatura. / Radiologic follow-up of early postoperative conditions of patients operated of chloridropeptic ulcer by vagotomy partial antrectomy and gastroduodenal anastomosis at the lesser curvature

Foram estudados 91 pacientes portadores de ulcera cloridropeptica submetidos vagotamia, antrectomia e anastomose gastroduodenal ao nivel da curvatura menor. O estudo foi realizado sobre o controle radiologico do transito gastro-intestinal dos pos-operatorios imediatos, visando observar o esvaziamento gastrico Verificamos que 64 pacientes apresentaram transito lento, sendo a maioria entre os operados por ulcera duodenal. Dezesete pacientes apresentaram transito normal. O transito rapido foi presente em dois pacientes. Finalmente, 8 pacientes tiveram obstrucao funcional de boca anastomotica, sendo 7 destes operados por ulcera duodenal com estenose pilorica

Estudo da motilidade de segmentos isolados do estomago, antes e apos antrectomia e anastomose gastroduodenal ao nivel da curvatura menor e em estomados nao operados de caes. / Motility of the isolated segments of the stomach, before and after antrectomy and gastroduodenal anastomosis at the level of the smaller curvature and in non-operated stomachs

Foram estudados segmentos gastricos de 45 caes divididos em tres grupos: 5 caes nao operados e 40 operados e acompanhados, 20 em pos-operatorio imediato e 20 em tardio.A cirurgia realizada foi antrectomia parcial e anastomose gastroduodenal ao nivel da curvatura menor. Estudou-se a motilidade espontanea de segmentos retirados da cardia, fundo, curvatura menor e maior do corpo e curvatura menor e maior do antro, montados em banhos para orgaos isolados.Encontraram-se dois tipos de contracoes: a classicamente denominada onda, que e fasica, e a contracao tonica continua. As ondas foram divididas em I, II e III, enquanto as contracoes tonicas dividiram-se em simples e segmentares. As ondas estiveram presentes em todos os segmentos com excecao dos retirados do fundo gastrico, enquanto as contracoes tonicas predominaram nestes segmentos. Verificamos que a cirurgia apresentada altera pouco a motilidade dos segmentos gastricos, tendo-se encontrado pequenas alteracoes, entre eles nas variaveis estudadas: amplitude, duracao e frequencia. O remanescente gastrico tendeu a demonstrar uma adaptacao motora no sentido de talvez melhorar sua condicao de esvaziamento (antrizacao?)

Controle radiologico do esvaziamento gastrico nos pos-operatorios imediato e tardio em pacientes submetidos a vagotomia, antrectomia e gastroduodenostomia na pequena curvatura. / Radiological control of gastric emptying in early and late postoperative periods in patients subjected to vagotomy, antrectomy and gastroduodenostomy in the smaller curvature

Fez-se o estudo radiologico pos-operatorio imediato e tardio de vagotomia, antrectomia e anastomose gastroduodenal na curvatura menor, em 47 pacientes portadores de ulcera cloridro-peptica. O esvaziamento gastrico foi analisado de acordo com o criterio de rapido, normal, lento e obstruido. Os autores observaram que os estomagos operados por ulcera gastrica nao apresentaram disturbios motores graves, enquanto nos com ulcera duodenal, encontraram uma hipotonia mais acentuada, no pos-operatorio imediato, que se normalizava tardiamente